Two problems under investigation are the mechanisms underlying neutralization of viruses by antibody, and the uncoating of viral genome that occurs early in infection. Recent preliminary studies have indicated that uncoating is a 2- stage reaction: weakening of the protein structure, followed by dispersal of the protein. A working hypothesis is that weakening occurs as a result of virus interacting with the cell's plasma membrane, and dispersal occurs when virus penetrates into the cell's interior. Attempts are under way to isolate from susceptible cells separate fractions having either weakening or dispersing activity. Availability of such an isolated system should enable characterization of the uncoating reactions, and reveal the temporal and spatial aspects of in vivo uncoating. The protein coat of poliovirus exists in either of two interconvertible conformations. When virus reacts with antibody, it not only loses infectivity but also becomes stabilized in one of the conformations. Studies are in progress to determine if stabilization is the cause of the loss of infectivity, or if it is a concomitant, but irrelevant effect. Both studies are being carried out with the poliovirus. Positive findings will be examined for generality by examining other viruses, closely or distantly related.